BI-3406
Based on 12 publication(s) in Google Scholar
BI-3406 (compound I-6) is an orally active, highly potent and selective inhibitor of the interaction between KRAS and Son of Sevenless 1 (SOS1) with an IC50 of 6 nM. BI-3406 potently reduces the formation of GTP-loaded KRAS, and inhibits MAPK pathway signaling. BI-3406 has anticancer activity.
For research use only. We do not sell to patients.
The BI-3406 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
- Purity: 99.95%
- CAS No.: 2230836-55-0
- Formula: C23H25F3N4O3
- Molecular Weight:462.46
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Storage:
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications Citing Use of MedChemExpress (MCE) BI-3406
More- Cancer Cell. 2025 Jul 25:S1535-6108(25)00310-1. [Abstract]
- Cancer Cell. 2024 Jul 8;42(7):1286-1300.e8. [Abstract]
- Nat Cancer. 2023 Jun;4(6):829-843. [Abstract]
- Cancer Res. 2025 Jan 2;85(1):101-117. [Abstract]
- Cell Commun Signal. 2025 Mar 3;23(1):116. [Abstract]
- Clin Cancer Res. 2021 May 1;27(9):2533-2548. [Abstract]
- Acta Pharmacol Sin. 2023 Jul;44(7):1475-1486. [Abstract]
- Cell Rep. 2023 May 29;42(6):112570. [Abstract]
- RSC Med Chem. 2024 Mar 15;15(4):1392-1403. [Abstract]
- iScience. 2026 Jun 17;29(7):116430. [Abstract]
- bioRxiv. 2025 Jan 24:2025.01.22.634215. [Abstract]
- bioRxiv. 2023 Oct 6.
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Cell Migration/Invasion Assay
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WB
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Cell Proliferation/Viability Assay
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In Vivo Efficacy Study
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Cell Imaging/Staining
Biological Activity
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KRAS-SOS1 6 nM (IC50) |
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| A549 | IC50 |
106 nM
Compound: 1; BI-3406
|
Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell growth
Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell growth
|
[PMID: 38714262] |
| A549 | IC50 |
263 nM
Compound: BI-3406
|
Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human A549 cells harboring KRAS G12S mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| ASPC1 | IC50 |
64.4 nM
Compound: BI-3406
|
Antiproliferative activity against human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human ASPC1 cells harboring KRAS G12D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| DLD-1 | IC50 |
102 nM
Compound: BI3406
|
Antiproliferative activity against human DLD-1 cells harboring G13D mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
Antiproliferative activity against human DLD-1 cells harboring G13D mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
|
[PMID: 38206836] |
| DLD-1 | IC50 |
169 nM
Compound: 1; BI-3406
|
Antiproliferative activity against human DLD-1 cells harboring KRAS G13D mutant assessed as inhibition of cell growth
Antiproliferative activity against human DLD-1 cells harboring KRAS G13D mutant assessed as inhibition of cell growth
|
[PMID: 38714262] |
| K562 | IC50 |
1.422 μM
Compound: BI-3406
|
Antiproliferative activity against human K562 cells incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human K562 cells incubated for 72 hrs by CCK8 assay
|
[PMID: 38316747] |
| K562 | IC50 |
37 nM
Compound: 6; BI-3406
|
Antiproliferative activity against human K562 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
Antiproliferative activity against human K562 cells assessed as reduction in cell viability measured after 72 hrs by CellTiter-Glo luminescent cell viability assay
|
[PMID: 37778239] |
| LoVo | IC50 |
142 nM
Compound: BI-3406
|
Antiproliferative activity against human LoVo cells harboring KRAS G13D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human LoVo cells harboring KRAS G13D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| MIA PaCa-2 | IC50 |
24.8 nM
Compound: BI-3406
|
Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human MIA PaCa-2 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| MIA PaCa-2 | IC50 |
29 nM
Compound: BI-3406
|
Antiproliferative activity against human MIA PaCa-2 cells incubated for 72 hrs by CCK8 assay
Antiproliferative activity against human MIA PaCa-2 cells incubated for 72 hrs by CCK8 assay
|
[PMID: 38316747] |
| MIA PaCa-2 | IC50 |
30 nM
Compound: 4; BI-3406
|
Antiproliferative activity against human MIA PaCa-2 cells harboring G12C mutant assessed as cell growth inhibition incubated for 7 days by Celltiter-Glo 3D cell viability assay
Antiproliferative activity against human MIA PaCa-2 cells harboring G12C mutant assessed as cell growth inhibition incubated for 7 days by Celltiter-Glo 3D cell viability assay
|
[PMID: 36793426] |
| NCI-H358 | IC50 |
16.5 nM
Compound: BI-3406
|
Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| NCI-H358 | IC50 |
24 nM
Compound: BI3406
|
Antiproliferative activity against human NCI-H358 cells assessed as reduction in cell viability
Antiproliferative activity against human NCI-H358 cells assessed as reduction in cell viability
|
[PMID: 38206836] |
| NCI-H358 | IC50 |
26 nM
Compound: BI3406
|
Antiproliferative activity against human NCI-H358 cells assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
Antiproliferative activity against human NCI-H358 cells assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
|
[PMID: 38206836] |
| NCI-H358 | IC50 |
26 nM
Compound: BI3406
|
Antiproliferative activity against human NCI-H358 cells harboring G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
Antiproliferative activity against human NCI-H358 cells harboring G12C mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
|
[PMID: 38206836] |
| NCI-H358 | IC50 |
90 nM
Compound: 2; BI-3406
|
Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 5 days by celltiter-glo 3D assay
Antiproliferative activity against human NCI-H358 cells harboring KRAS G12C mutant assessed as inhibition of cell proliferation incubated for 5 days by celltiter-glo 3D assay
|
[PMID: 38894918] |
| NCI-H441 | IC50 |
68 nM
Compound: BI3406
|
Antiproliferative activity against human NCI-H441 cells harboring G12V mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
Antiproliferative activity against human NCI-H441 cells harboring G12V mutant assessed as inhibition of cell proliferation incubated for 7 days by celltiter-glo 3D assay
|
[PMID: 38206836] |
| PANC-1 | IC50 |
17.8 nM
Compound: BI-3406
|
Antiproliferative activity against human PANC-1 cells harboring KRAS G12D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human PANC-1 cells harboring KRAS G12D mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| PC-3 | IC50 |
1.37 μM
Compound: BI-3406
|
Synergistic antiproliferative activity against human PC-3 cells assessed as inhibition of cell growth incubated for 72 hrs in presence of gefitinib by MTT assay
Synergistic antiproliferative activity against human PC-3 cells assessed as inhibition of cell growth incubated for 72 hrs in presence of gefitinib by MTT assay
|
[PMID: 38630077] |
| PC-3 | IC50 |
8.75 μM
Compound: BI-3406
|
Antiproliferative activity against human PC-3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
Antiproliferative activity against human PC-3 cells assessed as inhibition of cell growth incubated for 72 hrs by MTT assay
|
[PMID: 38630077] |
| SW-620 | IC50 |
30.1 nM
Compound: BI-3406
|
Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant assessed as inhibition of cell proliferation incubated for 7 days by CellTiterGlo-3D proliferation assay
|
[PMID: 36897932] |
| SW-620 | IC50 |
50.5 nM
Compound: 1; BI-3406
|
Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant assessed as inhibition of cell growth
Antiproliferative activity against human SW620 cells harboring KRAS G12V mutant assessed as inhibition of cell growth
|
[PMID: 38714262] |
BI-3406 is an inhibitor of the interaction between KRAS and its Guanine Nucleotide Exchange Factor (GEF) SOS1. BI-3406 does not block the interaction of KRAS with SOS2 but elicits activity on a broad panel of KRAS oncogenic variants, including all major G12 and G13 oncoproteins. Down-modulation of this signaling cascade by BI-3406 in KRAS G12 or G13 mutant cells effectively limits cell proliferation[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 2230836-55-0
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Appearance Solid
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Molecular Weight 462.46
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Formula C23H25F3N4O3
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Color White to off-white
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SMILES
CC1=NC(N[C@@H](C2=CC(C(F)(F)F)=CC(N)=C2)C)=C3C=C(O[C@@H]4COCC4)C(OC)=CC3=N1
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, stored under nitrogen
* In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
Publications (12)
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Journal Impact Factor
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Most Recent
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Cancer Cell
A pan-KRAS inhibitor and its derived degrader elicit multifaceted anti-tumor efficacy in KRAS-driven cancers. [Abstract]2025 Jul 25:S1535-6108(25)00310-1. PMID: 40780213 -
Cancer Cell
Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer. [Abstract]2024 Jul 8;42(7):1286-1300.e8. PMID: 38942026 -
Nat Cancer
Scribble mis-localization induces adaptive resistance to KRAS G12C inhibitors through feedback activation of MAPK signaling mediated by YAP-induced MRAS. [Abstract]2023 Jun;4(6):829-843. PMID: 37277529 -
Cancer Res
Targeted Degradation of SOS1 Exhibits Potent Anticancer Activity and Overcomes Resistance in KRAS-Mutant Tumors and BCR-ABL-Positive Leukemia. [Abstract]2025 Jan 2;85(1):101-117. PMID: 39437162
BI-3406 purchased from MedChemExpress. Usage Cited in: Cancer Res. 2025 Jan 2;85(1):101-117. [Abstract]
Western blot analysis of SOS1, pERK, GSPT1, and IKZF1/3 in NCI-H358 cells treated with SIAIS562055, SIAIS562092, or BI-3406 (10, 100, 1000 nM) for 24 hours.
BI-3406 purchased from MedChemExpress. Usage Cited in: Cancer Res. 2025 Jan 2;85(1):101-117. [Abstract]
Antiproliferative effects of SIAIS562055 and BI-3406 for 120 hours on KRAS-WT (293T, BxPC-3) and KRAS-mutant (NCI-H358, GP2d, HPAF-II, and SW620) cells.
BI-3406 purchased from MedChemExpress. Usage Cited in: Cancer Res. 2025 Jan 2;85(1):101-117. [Abstract]
MIA PaCa-2–xenografted mice received vehicle, SIAIS562055 (20 or 40 mg/kg/day), or BI-3406 (50 mg/kg, twice a day), then relative tumor weights were determined at indicated times.
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Cell Commun Signal
Sos1 ablation alters focal adhesion dynamics and increases Mmp2/9-dependent gelatinase activity in primary mouse embryonic fibroblasts. [Abstract]2025 Mar 3;23(1):116. PMID: 40033301
BI-3406 purchased from MedChemExpress. Usage Cited in: Cell Commun Signal. 2025 Mar 3;23(1):116. [Abstract]
Vehicle- (DMSO) or BI-3406-treated (1 µM) confluent WT primary MEFs were scratched with a micropipette tip and closure of the wounded area was recorded for 24 h by phase-contrast photomicroscopy.
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Clin Cancer Res
2021 May 1;27(9):2533-2548. PMID: 33619172 -
Acta Pharmacol Sin
143D, a novel selective KRASG12C inhibitor exhibits potent antitumor activity in preclinical models. [Abstract]2023 Jul;44(7):1475-1486. PMID: 36725884
BI-3406 purchased from MedChemExpress. Usage Cited in: Acta Pharmacol Sin. 2023 Jul;44(7):1475-1486. [Abstract]
MIA PaCa-2 or NCI-H1373 cells were treated with 143D or a combination of drugs and stained with crystal violet for identifying monoclonal cell populations. 143D (10 nM), BI3406 (10 μM), trametinib (5 nM), SCH772984 (200 nM), Afatinib (10 nM).
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Cell Rep
Kinetics of RTK activation determine ERK reactivation and resistance to dual BRAF/MEK inhibition in melanoma. [Abstract]2023 May 29;42(6):112570. PMID: 37252843 -
RSC Med Chem
2024 Mar 15;15(4):1392-1403. PMID: 38665844 -
iScience
Serum SOS1 as a prognostic biomarker and therapeutic target for progressive liver disease. [Abstract]2026 Jun 17;29(7):116430. PMID: 42369045 -
bioRxiv
Adaptive Plasticity Tumor Cells Modulate MAPK-Targeting Therapy Response in Colorectal Cancer. [Abstract]2025 Jan 24:2025.01.22.634215. PMID: 39896605 -
Solvent & Solubility
DMSO : 100 mg/mL (216.23 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Ethanol : 100 mg/mL (216.23 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: 2.5 mg/mL (5.41 mM); Clear solution; Need ultrasonic
This protocol yields a clear solution of 2.5 mg/mL.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Add each solvent one by one: 10% EtOH 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (5.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% EtOH 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (5.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Add each solvent one by one: 10% EtOH 90% Corn Oil
Solubility: ≥ 2.5 mg/mL (5.41 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.
Please enter the basic information of animal experiments:
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-
-
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL. * In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen)
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (stored under nitrogen). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO / Ethanol | 1 mM | 2.1623 mL | 10.8117 mL | 21.6235 mL | 54.0587 mL |
| 5 mM | 0.4325 mL | 2.1623 mL | 4.3247 mL | 10.8117 mL | |
| 10 mM | 0.2162 mL | 1.0812 mL | 2.1623 mL | 5.4059 mL | |
| 15 mM | 0.1442 mL | 0.7208 mL | 1.4416 mL | 3.6039 mL | |
| 20 mM | 0.1081 mL | 0.5406 mL | 1.0812 mL | 2.7029 mL | |
| 25 mM | 0.0865 mL | 0.4325 mL | 0.8649 mL | 2.1623 mL | |
| 30 mM | 0.0721 mL | 0.3604 mL | 0.7208 mL | 1.8020 mL | |
| 40 mM | 0.0541 mL | 0.2703 mL | 0.5406 mL | 1.3515 mL | |
| 50 mM | 0.0432 mL | 0.2162 mL | 0.4325 mL | 1.0812 mL | |
| 60 mM | 0.0360 mL | 0.1802 mL | 0.3604 mL | 0.9010 mL | |
| 80 mM | 0.0270 mL | 0.1351 mL | 0.2703 mL | 0.6757 mL | |
| 100 mM | 0.0216 mL | 0.1081 mL | 0.2162 mL | 0.5406 mL |